COMBINATION CHEMOTHERAPY FOR METASTATIC OR RECURRENT CARCINOMA OF THEBREAST - A RANDOMIZED PHASE-III TRIAL COMPARING CAF VERSUS VATH VERSUS VATH ALTERNATING WITH CMFVP - CANCER AND LEUKEMIA GROUP-B STUDY-8281

Purpose: We sought to compare three doxorubicin based therapies for me tastatic breast cancer for response frequency, time to treatment failu re (TTF), and survival. Materials and Methods: Women with metastatic b reast cancer who had measurable disease, required laboratory tests, ha d received no prior chemotherapy for metastases, had a Cancer and Leuk emia Group B (CALGB) performance status less than or equal to 2, and p rovided informed consent were eligible. Treatment included the followi ng: arm I-cyclophosphamide, doxorubicin, and fluorouracil (CAF); arm I I-vinblastine, doxorubicin, thiotepa, and halotestin (VATH); and arm I II-VATH alternating with cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) on cycles 3, 5, 7, 9, etc. Doses were modified for toxicities. Standard CALGB response and toxicity cri teria were used. Results: Between August 1982 and February 1987, 497 w omen were entered and 491 were treated on study. Pretreatment characte ristics were well balanced and the median follow-up duration was 79 mo nths. There were no significant differences in response (complete [CR] plus partial [PR]) at 50% on arm I, 57% on arm II, and 51% on arm III . The median TTFs were 8, 8, and 9 months, respectively, in favor of a rm ill when compared with arm I (P = .028). The median survival times for treatment arms I, II, and III were 15, 17, and 17 months, respecti vely. After multivariate regression analyses, only estrogen receptors (ER), performance status, and number of metastatic sites influenced TT F and survival. Leukopenia was the most common grade 3 or 4 toxicity, occurring in 90%, 80%, and 92% of patients per arm, respectively, Leth al toxicities were seen in four, five, and six women, respectively. Ov erall, there were more grade greater than or equal to 3 toxicities on arm II than I, and most occurred on arm III (P = .02). Conclusion: The VATH regimen appears similarly effective to the CAF regimen as initia l therapy. Alternating CMFVP with VATH did not improve response rate o r survival. After accounting for other variables, treatment arm was no t related to outcome. New therapeutic regimens are still needed. (C) 1 995 by American Society of Clinical Oncology.